Nod2 deficiency is associated with an increased mucosal immunoregulatory response to commensal microorganisms.
Nod2 deficiency is associated with an increased mucosal immunoregulatory response to commensal microorganisms.
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DOI：
10.1038/mi.2013.58
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发表时间：
2014-03
影响因子：
8
通讯作者：
Boirivant M
中科院分区：
文献类型：
--
作者：
Amendola A;Butera A;Sanchez M;Strober W;Boirivant M
基于先前的研究表明结肠上皮屏障的破坏与LP调节细胞的微生物群依赖性增加有关，我们研究了在Nod 2 −/−小鼠中观察到的自发性肠道炎症的缺乏是否是由于肠道调节功能增强。我们发现，Nod 2 −/−小鼠的LP CD 4 + T细胞群中携带TGF-β/潜伏肽的CD 4+调节性T细胞（LP CD 4 + T细胞）的百分比增加，无论是在基线条件下还是在乙醇给药诱导的结肠屏障故意破坏后。此外，我们发现Nod 2 −/−小鼠表现出TNBS-结肠炎的严重程度降低，并且Nod 2 −/−或Nod 2 +/+小鼠中的TNBS-结肠炎通过过继转移来自乙醇处理的小鼠的LP细胞而得到改善，但在耗尽Nod 2 + T细胞之前，而不是之后。Nod 2 −/−小鼠中调节性T细胞反应的增加可以解释为什么人类NOD 2多态性本身不足以建立炎症病变。
Based on previous studies demonstrating that a breach of the colonic epithelial barrier is associated with a microbiota-dependent increase in LP regulatory cells, we investigated if the lack of spontaneous intestinal inflammation observed in Nod2−/− mice was due to enhanced intestinal regulatory function. We found that the LP CD4+ T cell population of Nod2−/− mice contains an increased percentage of CD4+ regulatory T cells bearing TGF-β/latency peptide (LP CD4+LAP+ T cells) both under baseline conditions and following an intentional breach of the colonic barrier induced by ethanol administration. In addition, we found that Nod2−/− mice manifest decreased severity of TNBS-colitis and that TNBS-colitis in Nod2−/− or Nod2+/+ mice is ameliorated by adoptive transfer of LP cells from ethanol-treated mice before, but not after, depletion of LAP+ T cells. This increased regulatory T cell response in Nod2−/− mice could explain why NOD2 polymorphisms in humans are not in themselves sufficient to establish inflammatory lesions.